Secretion of enkephalin-like peptides immunoreactive to (met5) or (leu5-enkephaline from adrenal glands into circulation was studied in dogs with indwelling cannulae in the lumbar adrenal vein. The stimulation of the splanchnic nerve causes a voltage-dependent increase in met-enkephaline immunoreactive peptides in adrenal venous plasma. The peptide secreted from adrenal gland was identified to be met-enkephalin by Bio-Gel P-2 chromatography followed by high performance liquid chromatography. Injection of morphine also increased the plasma content of these peptides which was blocked by naloxone and hexamethonium. The effect of splanchnic nerve stimulation was mimicked by dimethylphenylpiperazinium and could be blocked by hexamethonium. This study clearly indicates that the release of met-enkephalin-like peptides from adrenal glands is mediated through activation of nicotinic receptors.